Monosynaptic reflex

Physiology G6001 Nerve and Synapse Classical elements of synaptic transmission: Neuromuscular junction Transmitter release Synaptic currents Synaptic potentials Nerve-nerve synapses Synaptic integration Summation Facilitation Amy MacDermott, Department of Physiology and Cellular Biophysics and the Center for Neurobiology and Behavior phone

Schematic of the NMJ

The Neuromuscular Junction

Physiology G6001 Nerve and Synapse Classical elements of synaptic transmission: Neuromuscular junction Transmitter release Synaptic currents Synaptic potentials Nerve-nerve synapses Synaptic integration Summation Facilitation

Exocytosis and transmitter release at the nerve terminal

Protein machinery for vesicle release Rizo and Sudhof Nature Reviews Neuroscience 3; (2002);

Key elements of transmitter release

Recording from the neuromuscular junction (NMJ). Spontaneous release of a vesicle of Ach causes a miniature endplate potential or MEPP Evoked release following stimulation of the motor neuron causes an endplate potential or EPP

Presynaptic calcium channels at the neuromuscular junction (NMJ)

Pre and postsynaptic changes in membrane potential during transmitter release

Recording from the neuromuscular junction (NMJ). Spontaneous release of a vesicle of Ach causes a miniature endplate potential or MEPP Evoked release following stimulation of the motor neuron causes an endplate potential or EPP

The quantal nature of transmitter release. Decrease the amplitude of evoked release by recording in low Ca2+ bath.

Physiology G6001 Nerve and Synapse Classical elements of synaptic transmission: Neuromuscular junction Transmitter release Synaptic currents Synaptic potentials Nerve-nerve synapses Synaptic integration Summation Facilitation

NMJ – an inward current drives the change in membrane potential

Membrane potential and driving force– brief review Vm= (RT/F) ln [K] o /[K] i Vm= (RT/F) ln Na] o /[Na] i

Reversal potential ____________ I EPSP = g EPSP x (Vm-E EPSP )

Membrane time constant – a review

Synaptic potential is not actively propagated

ACh binds to the nicotinic ACh receptor, causing it to gate open. The channel is permeable to both Na + and K +. The end-plate potential causes voltage gated Na + channels to open and an action potential to fire.

An EPP in normal muscle is super-threshold for firing action potential

Physiology G6001 Nerve and Synapse Classical elements of synaptic transmission: Neuromuscular junction Transmitter release Synaptic currents Synaptic potentials Nerve-nerve synapses Synaptic integration Summation Facilitation

Heuser and Reese – two synapses in the cerebellum

Classes of neurotransmitter receptors OUT IN + - IONOTROPICMETABOTROPIC   

Excitatory synaptic transmission is mediate by glutamate receptors NMDA receptors (NMDARs) AMPA receptors Kainate receptors metabotropic Glu receptors OUT IN GLU, NMDA GLU, KA K+K+ K+K+ Na +, Ca 2 + Na +, (Ca 2+ ?) GLU GLU, KA    

Current-voltage relationship for synaptic currents mediated by AMPA and NMDA receptors

Inhibitory synaptic transmission is mediated by GABA and glycine receptors

Physiology G6001 Nerve and Synapse Classical elements of synaptic transmission: Neuromuscular junction Transmitter release Synaptic currents Synaptic potentials Nerve-nerve synapses Synaptic integration Summation Facilitation

Membrane time constant – a review

What determines the time course of the synaptic potential?

Temporal summation depends on the passive membrane properties of the neuron or muscle Tau or  = C x R

Summation is postsynaptic while facilitation is usually presynaptic

Summation of EPSP and IPSP

The trigger zone

The synaptic potential is not actively propagated. The rate of decay with distance is exponential:  V(x) =  V 0 e -x/  and ~ (r m /r a )

Different synaptic configurations including axo-somatic, axodendritic and axo-axonic

Implications of synapse location Length constant  Rm/Ra

Temporal and spatial summation: importance of time constant  and length constant

Three forms of modulation of synaptic transmission mediated by metabotropic receptors

Berne and Levy – chapter 4 or Kandel, Schwartz, and Jessell – chapters 11 and 12 or Kandel, Schwartz, and Jessell – chapters 10-15

Recording from the neuromuscular junction (NMJ). Spontaneous release of a vesicle of Ach causes a miniature endplate potential or MEPP Evoked release following stimulation of the motor neuron causes an endplate potential or EPP

The reversal potential is determined by the concentrations of ions flowing through the synaptic channel.